Inflammatory cytokine-mediated evasion of virus-induced tumors from NK cell control
UMass Chan AffiliationsDepartment of Pathology
Document TypeJournal Article
Cell Line, Tumor
Killer Cells, Natural
Mice, Inbred C57BL
NK Cell Lectin-Like Receptor Subfamily K
Nuclear Matrix-Associated Proteins
Nucleocytoplasmic Transport Proteins
Salivary Gland Neoplasms
Tumor Necrosis Factors
Tumor Virus Infections
Immunology and Infectious Disease
MetadataShow full item record
AbstractInfections with DNA tumor viruses, including members of the polyomavirus family, often result in tumor formation in immune-deficient hosts. The complex control involved in antiviral and antitumor immune responses during these infections can be studied in murine polyomavirus (PyV)-infected mice as a model. We found that NK cells efficiently kill cells derived from PyV-induced salivary gland tumors in vitro in an NKG2D (effector cell)-RAE-1 (target cell)-dependent manner; but in T cell-deficient mice, NK cells only delay but do not prevent the development of PyV-induced tumors. In this article, we show that the PyV-induced tumors have infiltrating functional NK cells. The freshly removed tumors, however, lack surface RAE-1 expression, and the tumor tissues produce soluble factors that downregulate RAE-1. These factors include the proinflammatory cytokines IL-1alpha, IL-1beta, IL-33, and TNF. Each of these cytokines downregulates RAE-1 expression and susceptibility to NK cell-mediated cytotoxicity. CD11b(+)F4/80(+) macrophages infiltrating the PyV-induced tumors produce high amounts of IL-1beta and TNF. Thus, our data suggest a new mechanism whereby inflammatory cytokines generated in the tumor environment lead to evasion of NK cell-mediated control of virus-induced tumors.
SourceMishra R, Polic B, Welsh RM, Szomolanyi-Tsuda E. Inflammatory cytokine-mediated evasion of virus-induced tumors from NK cell control. J Immunol. 2013 Jul 15;191(2):961-70. doi: 10.4049/jimmunol.1203328. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/30147
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